A debate exists as to whether the output of the fetal heart is modulated by changes in ventricular volume, heart rate or inotropy. Two strikingly opposed viewpoints presently exist: only heart rate modulates fetal cardiac output versus only a change in end-diastolic volume modulates fetal cardiac output. This controversy extends to how neonatal cardiac output is modulated by these variables, and how the filling of one fetal ventricle alters the filing and ejection of the other. Three groups of lambs (two fetal groups 110-112 days and 126-132 days of gestation and one neonatal group 40-55 days of age) will be chronically instrumented with electromagnetic flow probes (the ascending aorta and the main pulmonary artery), catheters in the superior vena cava, left atrium, brachiocephalic trunk, pulmonary artery, right and left ventricle, and pleural and amniotic spaces, left ventricular micromanometer pressure transducer, electrocardiographic leads, right ventricular and left ventricular ultrasonic dimension transducers and bipolar right and left atrial pacing leads. The effect of heart rate on cardiac output will be described under two conditions: i) when the volume, inotropic state and afterload vary freely and ii) when these variables are the same at the various rates. Similarly, we will study the independent effect of each of these variables on cardiac output. In vitro measurements will determine the relationship among right and left ventricular volumes and end-diastolic dimension and pressure and will provide the basis for relating in vivo measurements of end-diastolic dimension and pressure to end-diastolic ventricular volume. By examining three different ages, developmental changes in the effect of variations in heart rate, volume and inotropic state on ventricular output can be sought. Only by understanding how cardiac output is modulated in the fetus and the neonate can we understand what the mechanisms are that permit the heart to adapt to birth and respond to perinatal stress. Resolving the present controversy as to how the right and left ventricular output are modulated at different points in development will provide the basis for a better evaluation of the ill premature and full-term infant and help in developing more successful therapeutic regimens.